title: β-Cyclodextrin inclusion complex to improve physicochemical properties of pipemidic acid: characterization and bioactivity evaluation.
abstract: The aptitude of cyclodextrins (CDs) to form host-guest complexes has prompted an increase in the development of new drug formulations. In this study, the inclusion complexes of pipemidic acid (HPPA), a therapeutic agent for urinary tract infections, with native β-CD were prepared in solid state by kneading method and confirmed by FT-IR and 1H NMR. The inclusion complex formation was also characterized in aqueous solution at different pH via UV-Vis titration and phase solubility studies obtaining the stability constant. The 1:1 stoichiometry was established by a Job plot and the inclusion mechanism was clarified using docking experiments. Finally, the antibacterial activity of HPPA and its inclusion complex was tested on P. aeruginosa, E. coli and S. aureus to determine the respective EC50s and EC90s. The results showed that the antibacterial activity of HPPA:β-CD against E. coli and S. aureus is higher than that of HPPA. Furthermore, HPPA and HPPA:β-CD, tested on human hepatoblastoma HepG2 and MCF-7 cell lines by MTT assay, exhibited, for the first time, antitumor activities, and the complex revealed a higher activity than that of HPPA. The use of β-CD allows an increase in the aqueous solubility of the drug, its bioavailability and then its bioactivity.
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Via A. Vivaldi 43, 81100 Caserta, Italy. rosa.iacovino@unina2.it.
authors.forename: Rosa
authors.initials: R
authors.lastname: Iacovino
authors.forename: Filomena
authors.initials: F
authors.lastname: Rapuano
authors.forename: Jolanda Valentina
authors.initials: JV
authors.lastname: Caso
authors.forename: Agostino
authors.initials: A
authors.lastname: Russo
authors.forename: Margherita
authors.initials: M
authors.lastname: Lavorgna
authors.forename: Chiara
authors.initials: C
authors.lastname: Russo
authors.forename: Marina
authors.initials: M
authors.lastname: Isidori
authors.forename: Luigi
authors.initials: L
authors.lastname: Russo
authors.forename: Gaetano
authors.initials: G
authors.lastname: Malgieri
authors.forename: Carla
authors.initials: C
authors.lastname: Isernia
mesh_terms: D002152:Calorimetry, Differential Scanning; D003505:Cyclodextrins / Q000737:chemistry; D004926:Escherichia coli; D006801:Humans; D010876:Pipemidic Acid; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013211:Staphylococcus aureus; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D003505:Cyclodextrins; D047392:beta-Cyclodextrins; D010876:Pipemidic Acid